International Journal of Generic Drugs

ISSN 0793 7601 - ISSN 0793 761X
Series Publication in association with:-

Handbook of
Pharmaceutical GenericDevelopment
The International Association ofGeneric Drug Manufacturers

Oral IR

TabletsPart

ONE

DRUG DEVELOPMENT KNOW-HOW

&

Part

TWO

ANDA DEVELOPMENT & FORMULATIONSNEW Edition
Year 2001

Handbook Volume in Part I & II

Drug Development

Handbook of Pharmaceutical GenericDevelopment a comprehensive andauthoritative practical hands-on state-ofthe-art handbook covering Generic knowhow essential for developing the 21 ANDA
Sections of an Immediate Release Oral
Tablet.
Part One covers Pharmaceutical Drug
Development and Part Two (ANDA
Development) providing know-how for
Development, Excipient and specification
choice, Formulation, Dissolution, Stability,
Scale-up, Process Qualification (Hardness
Dissolution & U of C); Pivotal and final
validation batches; Analytical, Cleaning andProcess Validation; Incorporates essential
development
checklists,
flowcharts,
tabulations and key SOPs and critical
documentation and OGD regulatory knowhow for a successful review for a FDA
approval, saving queue-time and money.
Essential development and submission
know-how on Immediate Release Oral
Tablets for professional developers tounderstand the nuts-and-bolts on Generic
ANDA DEVELOPMENT with high-techdetailed ANDA Development (new formula &guidelines) for rapid flawless approval of
ANDA submissions(Print or CD ROM).
Some Additional Titles:-

ANDA DEVELOPMENT
Locum International
Locum Publishing House

Bupropion, BuspIrone, Diclofenac, Famotidine,
Felodipine, Nabumetone, Naproxin, Piroxicam,
Tamoxifen US/EU, Ticlopidine, Trazodone etc.
E-mail:handbooks@l o c u m u s a . c o m

Fax Int.: + 972-97-494-532
Fax US: +(1)-435-408-1665
Fax UK: +(44)-207-900-2096
A Locum House Publication - ©Copyright Locum 1996-2000

http://www.locumusa.com
International Journalof Generic Drugs
e-* info@locumusa.com
ISSN 0793 694X US/Canada
ISSN 0793 7784 EuroISSN 0793 7822 Pacific Rim

International Journal of Generic Drugs

ORAL DOSAGE FORMS
Table of Content - Summary
PART I - PHARMACEUTICAL DEVELOPMENT

Typical - Oral Tablet or Capsule
Acronyms - Abbreviations
Introduction, Preface & Forward
Chapter
1
Regulatory- Pre-formulation Checklist
Documentation- SOP Control Checklist
Development Notebooks- Development Notebooks Checklist- SOP Control and Development Notebooks SOPs
Chapter2
Developing the Formula -an Overview- Formulation Checklist- Key Generic Development formulations
Drug Development Checklist (Top Generics )Development Formula for today's top Generics
Developing the generic Formula
Product Development Flow Chart
Product Development Guide - Tips & Traps
Purified Water - an essential ingredient
Do and Don'ts in Development
Purified Water - Checklist
Chapter3
Active Ingredients-Do’s and Don’ts-Active development Checklist-Approved Suppliers Checklist-Standard Operating Procedures, Actives
Chapter
4
Semi active ingredients-Validating the Semi-active ingredients, Checklist
Qualifying the Antioxidant - Protocol & Procedure
Antioxidant Tabulations & Documentation
Chapter5
Non active materials (excipients)-Checklist non active ingredient & FDA IIG list
-Standard Operating Procedures, Non actives
Chapter
6
Container closure systems-Container-liner-closure systems, Checklist-Container-liner-closure systems, Key SOPs
-Packaging Components - rules & regulations-Packaging Components Documentation Requirements SOP
Chapter
7
Manufacturing Process & Instructions from A to Z
- Wet, Dry, Spray Granulation- Aqueous & alcoholic granulation- Dry Mixing and Slugging- Manufacturing Instructions; Checklist- The manufacturing Instructions and Controls- Manufacturing Flow Charts and Diagrams- Large scale manufacturing Instructions- Large scale Master Formula and Processes -key generics- Large scale Manufacturing Instructions
Chapter8
In-process Quality Controls-Manufacturing in-process controls; Checklist-In-process Quality Controls; SOPs
Chapter
9
Finished Product Specifications- Finished Product Specifications example and Checklist- Release & Check Specifications- Finished Product Specifications; Required SOPs
Chapter
Qualification of Antioxidant and Lubricant
Process Optimization and Procedures
Qualification of Loss on Drying Limits
Chapter
11
Scale-up Procedures know-how- Scale-up procedures; checklist- Scale-up procedures; SOPs

Chapter
12
Cleaning Procedures, guidelines & Limits
Cleaning Limits Procedures; Checklist
Cleaning Validation Requirements; SOPs
Chapter
13
Analytical Validation Requirements-Analytical Testing Out of Specification-Analytical Testing Do's and Don'ts-Ruggedness and Robustness-Impurities in Drug Substances-Impurities Do's and Don'ts-Impurities Glossary of Terms-Impurities Decision Trees
Analytical Post approval Changes -PAC-ALTS
PAC-ALTS Checklist
Chapter
14
Process Qualification Batch Know-how-Process Qualification Batch; Checklist-Process Qualification Batch; SOPs
-Process Qualification Blend Analysis and - Do's and Don'ts-Process Qualification Content Uniformity or Tablet Hardness
Content Uniformity or Tablet Hardness Protocol
Chapter
15
Pivotal batch Operation & Process from A to Z
-The Pivotal Batch regulatory requirements-Pivotal batch Checklist & Do's and don'ts-Pivotal batch Critical SOPs, Tips & Traps-Sampling and Testing the Pivotal Batch-Auditing the Pivotal batch - Tablulations-Auditing the Pivotal batch - Checklist
Chapter
16
Bioequivalence vs. RLD
Test Designs - Overview
Statistical Bioequivalence
IBE Equation explained
IBE Big Picture (Pros and Cons)
Comparing IBE and ABE
Typical IVIVC Models
Choosing IVIVC levels
Dissolution Testing in IR Dosage Forms
Similarity Factor in dissolution testing
BSC and Biowaivers
Overall Dissolution Picture
Biopharmaceutics Classification System
Performance Verification in Dissolution testingFood-Effects in BA-BE Studies
Similarity Testing - Chow, Pitt and Others
Chapter
17
Technical Transfer Documentation-Technical Transfer Documentation; Checklist-Technical Transfer Documentation; Pharmaceutical Part
-Technical Transfer Documentation; Analytical Part
Chapter
18
The Process Validation Batch - Tips & Traps-The Process Validation Batches; Checklist-Process Validation Requirements; SOPs
-Process Validation Master Plan & Protocols
Chapter19
Pre--Approval Inspections
PAI SummaryPre--Approval Inspection Audit - Team Set Up
Pre--Approval Inspection Audit - Team Activities
Chapter
20
Stability Testing of Drug Substance and Drug Product I
Stability Testing of Drug Substance and Drug Product II
Stability Testing of Drug Substance and Drug Product II
Stability Testing Significant Change
Storage Conditions
Setting up a functional Stability Unit
Stability SOPs Development
Chapter
21
10Standard Operational Procedures
Development SOPs ; Stability SOP Network
Index of Pharmaceutical Standard Operating Procedures
Index of Analytical Standard Operating Procedures
Index of Microbiological Standard Operating Procedures
Index of Stability Standard Operating Procedures.

http://www.locumusa.com
International Journal of Generic Drugs
e-* info@locumusa.com
ISSN 0793 694X US/Canada
ISSN 0793 7784 EuroISSN 0793 7822 Pacific Rim

Handbook of Generic Drug Development -24 Volume Series

Handbook of

Pharmaceutical

Generic
Development
Handbook Drug Development Series
ISSN 0793 8772-

ISSN 0793 8780

Controlled

ReleaseExtended Solid Oral Dosage Forms

ONE

Part

Complete Drug Development Know-how

&

Part

TWO

ANDA Formula & Development Technology

READY-TO-GO™ SERIESFelodipine ER, Glipizide ER,
Sinemet ER, Naproxen DR,
Carbamazepine ER, Pentoxiphyllin ER

CONTROLLED RELEASE TABLETS

Extended & Modified
Release Dosage Forms

Tablets
This Handbook of Pharmaceutical GenericDevelopment is a fully comprehensive
practical hands-on workbook covering modern
drug development and the full 21 ANDA
section interactions of a Extended or Modified
Controlled Release Oral Tablets or Caplets.
Part One (drug development) and Part Two(ANDA Development Know-how) provide
Development, Master Drug Formulations, Key
Processes, Scale-up; Process Optimization &Qualification; Stability; Pivotal and final
Process Validation Know-how and Protocols;
PAI, Analytical, Cleaning and Process
Validation Do's & Don'ts. A reference for
critical documentation and OGD regulatory
know-how that is essential for a successful
first time FDA review and approval, saving
months ofqueue-time and market placesales.
Each and every regulatory guideline iscovered in clear detail providing adevelopment protocol for a totally omissionfree file submission.
Over five years in preparation and claimed as
the world's most authoritative and definitive
work available on oral dosage form drug
development from a generic industry
viewpoint.
An Essential Reference for Development
Pharmacists, R&D Chemists, QA/QC andRegulatory personnel. Allows management tounderstand the nuts and bolts on Generic
ANDA DEVELOPMENT and filing and how to
get to the market place - quickly and on time.
Locum Publishing House PO Box 16075 Arlington VA 22215 -1075 USA
A Locum House Publication - ©Copyright LOCUM 1996-2000

Circle 21
http://www.locumusa.com
International Journal of Generic Drugs
ISSN 0793 694X US/Canada
ISSN 0793 7784 Euroe-* info@locumusa.com
ISSN 0793 7822 Pacific Rim

Handbook of Generic Drug Development -ISSN 0793 7601 -ISSN 0793 761X

24 Volume Series Publicationin association with:-

24 Volume Series

Handbook of

Pharmaceutical
Generic
Development

Oral DR

The International Association ofGeneric Drug Manufacturers

Part

ONE

DRUG DEVELOPMENT KNOW-HOW

&

Part

TWO

ANDA DEVELOPMENT & FORMULATIONS

NEW 2001
EditionTablets

This Handbook of Pharmaceutical GenericDevelopment is a practical hands-on
workbook
covering
state-of-the-art
development for the full 22 ANDA
development sections required for a Oral
DR Tablet (Spay Granulation Enteric Coated
Delayed Release). About 450 pages.
Part One covers pharmaceutical drug
development and Part Two (ANDA
Development) provide technical know-howfortheDevelopment,
Formulation,
Dissolution, Stability, Scale-up, Process
Qualification; pivotal and final validationbatches; analytical, cleaning and processvalidation; essential documentation and OGD
regulatory know-how that is essential for a
successful first time FDA review and approval,saving months of queue-time and market
place sales.
Essential development and submission knowhow on Delayed Release Oral Tablets foradvanced
professional
developers
tounderstand the nuts-and-bolts on Delayed
Release DEVELOPMENT side-by-side withdetailed and practical ANDA development
technology for rapid approval of ANDA files(Print or CD ROM).

ANDA DEVELOPMENT

Title:- Handbook of Generic Drug Development
Delayed Release Tablets ISSN 0793-7601 / 0793-761X.
E-mail:- handbooks@locumusa.com

Locum International
Locum Publishing House

handbooks@locumEuro.com

Fax Int.: + 972-97-494-532
Fax US: +(1)-435-408-1665
Fax UK: +(44)-207-900-2096

A Locum House Publication - ©Copyright LOCUM 1996-2000

http://www.locumusa.com
International Journal of Generic Drugs
ISSN 0793 694X US/Canada
ISSN 0793 7784 Euroe-* info@locumusa.com
ISSN 0793 7822 Pacific Rim

Handbook of Generic Development-

A Series Publication in association withThe International Association of Generic Drug Manufacturers

24 Volume Series

Handbook of

Pharmaceutical
Locum International Publishers
ISSN 0793 8659 - ISSN 0793 8667

G e n e r i c
Development

Oral IR

CapsulesNEW 2001
EditionPartONE

DRUG DEVELOPMENT

&

Part

TWO

Regulatory ANDA Development[with master formula & commercial processes]

SINGLE ORAL DOSAGE FORM

The

Handbook of
Pharmaceutical
Generic Development is an essential
workbook covering the full development,
CMC and RA sections for a single dose
IR Capsule ANDA development project.

Part One (Drug Development ±500 pages)
and Part Two (ANDA Development withdetailed commercial and state-of-the-art
formula ±450 pages) provides essential IR
ADDITIONAL TITLES - in PART II
Amoxicillin 250 / 500mg;Azithromycin
250/600mg Cefaclor 250/500mg
Clomipramine 25/50/75mg
Etodolac 200/300 mg; Fluoxetine 10/20mg
Gabapentin 100/200/300mg
Piroxicam 10/20mg; Tolmetin 600 mg.

capsule technology know-how on all
aspects of; Development, Formulation,
Scale-up, Process Optimization &Qualification; Pivotal and large scale
Validation batches; analytical, cleaningand process validation; detailing crucial
documentation and OGD regulatory
know-how that is essential for a
successful review for FDA approval,saving queue-time and money. Full
Review of every CMC/Bio FDA guideline
issued.
Essential developmental know-how on Oral
IR Capsules for professional developers tounderstand the nuts-and-bolts on Generic
ANDA DEVELOPMENT with high-techpractical ANDA development know-how to
produce utterly flawless files. (Print & CD
ROM).

Locum International
Locum Publishing House
Fax + 972-97-494 532

ISSN 0793 694X US/Can

Technological Level - Advanced.
e-mail:- handbooks@locumusa.com
For Complete Table of Contents(Go to Web Site - www.iagim.org)

International Journal of Generic Drugs
ISSN 0793-7784 EuroISSN 0793-7822 Pacific Rim

Handbook of Generic Development-

Handbook of

Locum International Publishers
ISSN 0793 7407 - ISSN 0793 8756 - ISSN 0793 8764

A Series Publication in association withThe International Association of Generic Drug Manufacturers.

Oral ERONEDRUG DEVELOPMENTCAPSULES&Part

Pharmaceutical
Generic Development

NEW Advanced
2000-EditionPart

24 Volume Series

TWO

Regulatory ANDA Development

The

Each Volume Includes:

Development Handbook
ANDA Development[with master formula & commercial processes]

Handbook of Pharmaceutical
Generic Development is an essential
workbook
covering
theFullDevelopment, CMC and QA/RA sections
for a ER & SR [MR] CAPSULE
development program.
Part One (ER Development ±450 pages)
and Part Two (ANDA Development withdetailed commercial and state-of-the-art
MRformulaeandmanufacturing
processes ±350 pages) provides essential
ER Capsule Technology know-how on all
aspects of; Development, Formulation,
Scale-up, Process Optimization &Qualification; Pivotal and Large Scale
Validation batches using both pan and
Wurster Spray Granulators (GPCG
60/120); ER analytical methodology;
Dissolution, cleaning and processvalidation; essential documentation and
OGD Regulatory / R&D know-how,essential for a successful review & FDA
approval, saving queue-time and money.

Essential development know-how on Oral
ADVANCED ER & SR [MR]Formula & Manufacturing Details for CoatedSugar Spherical (bead) Technology
Coated Pellets and Coating Highly Soluble
Crystals (SR KCL 1200 mg, 20-40 mesh)Coating materials include Ethocel 100 HPMC;
Methocel; Dibutyl Sebacate; DEP etc,
Locum International
Locum Publishing House

ISSN 0793 694X US/Can

ER/SR Capsule for advanced developers tounderstand the nuts-and-bolts on Generic
MODIFIED RELEASE DEVELOPMENT witha high-tech detailed ANDA development toproduce flawless files. (Print & CD ROM).
Presented at an Advanced Technological Level.
E-mail: h a n d b o o k s @ l o c u m u s a . c o m
See Web Book shop or Fax+972-97-494 532
A Locum House Publication - © Copyright LOCUM 1995-2001.

handbooks@locumUSA.com

International Journal of Generic Drugs
ISSN 0793-7784 EuroISSN 0793-7822 Pacific Rim

International Journal of Generic Drugs
Locum International Publishers
ISSN 0793 8713 - ISSN 0793 8721

A Series Publication in association withThe International Association ofGeneric Drug Manufacturers.

NEW Edition
2001

Part

Handbook of

Pharmaceutical
Generic Development
ISBN 965 492 004-2

Oral

ONE

DRUG Development Know-how

&

Part

TWO

ANDA Development Technology

Suspensions
The Handbook of Pharmaceutical
Generic Development is an essential
workbook covering the full CMC & Bio
and RA sections of normal Oral
Suspension ANDA / AADA and a

Drug Development

Suspension for Reconstitution.
Part One (Development ISBN 965 492 0042) and Part Two (ANDA Development 965492005-0
withdetailedcommercial and state-of-the-art formula)provides essential know-how technology
on all aspects of; Development,
Formulation,
Scale-up,
Process
Optimization & Qualification; Pivotal and
large
scale
Validationbatches;analytical,
cleaning
andprocess
validation; essential documentation and
OGD regulatory know-how that isessential for a successful review for a
FDA approval, saving queue-time andmoney.

ISBN

ANDA Development

Cephalosporins
Synthetic Penicillins
Azithromycin
SMX-TMP(Cotrimoxazole)

Essential development know-how on Oral
Suspensions and Suspensions for
Reconstitution professional developers tounderstand the nuts-and-bolts on Generic
MODIFIED RELEASE DEVELOPMENT witha high-tech detailed ANDA development toproduce flawless files. (Print & CD ROM).
Presented at an Advanced Technological Level.
See Web Secure Book Shop or Fax+972-97-494 532

Locum International Press
Locum Publishing House

handbooks@locumUSA.com
A Locum House Publication©Copyright LOCUM 1995 - 2001

http://www.locum.co.il
International JournalofGeneric Drugs
e-* info@locum.co.il
ISSN 0793 694X US/Canada
ISSN 0793 7784 EuroISSN 0793 7822 Pacific Rim

Handbook of Generic Development-

A Series Publication in association withThe International Association ofGeneric Drug Manufacturers

24 Volume Series

Handbook of

PharmaceuticalG e n e r i c
Development
Locum International Publishers
ISSN 0793 8659 - ISSN 0793 8667

Soft Gelatin

NEW 2001
EditionPart

CapsulesONE

DRUG DEVELOPMENT

&

Part

TWO

Regulatory ANDA Development[with master formula & commercial processes]

The

Handbook of
Pharmaceutical
Generic Development is an essential
workbook covering the full development,
CMC and RA sections for a single dose
SG Capsule ANDA development project.

Part One (Drug Development ±500 pages)
and Part Two (ANDA Development withdetailed commercial and state-of-the-art
formula ±450 pages) provides essential

Soft Gelatin Capsules

Locum Publishing House
Fax US +435-808-1891
Global Fax +972-97-494 532
Fax UK +44-207-900-2096

ISSN 0793 694X US/Can

SG capsule technology know-how on all
aspects of; Development, Formulation,
Scale-up, Process Optimization &Qualification; Pivotal and large scale
Validation batches; analytical, cleaningand process validation; detailing crucial
documentation and OGD regulatory
know-how that is essential for a
successful review for FDA approval,saving queue-time and money. Full
Review of every CMC/Bio FDA guideline
issued.
Essential developmental know-how on Oral
SG Capsules for professional developers
to understand the nuts-and-bolts on Generic
ANDA DEVELOPMENT with high-techpractical ANDA development know-how to
produce utterly flawless files. (Print & CD
ROM).

Technological Level - Advanced.
e-mail:- handbooks@locumusa.com
For Complete Table of Contents(Go to Web Site - www.iagim.org)

International Journal of Generic Drugs
ISSN 0793-7784 EuroISSN 0793-7822 Pacific Rim

International Journal of Generic Drugs

Essential
Pharmaceutical

Generic D r u g

Development
Series ISSN 0793 8810 / Electronic 0793 8828

A Series Publication in association withThe International Association of Generic& Innovative Drug Manufacturers.

þPharmaceuticalþIQOQ & AnalyticalþDecision TreesþBioequivalencyþMicrobiologicalþQuality ControlþScale-UpþCleaning ProtocolsþAll ValidationsþRegulatoryþPre Approvals-PAIs
þAnnual Reports

e-SOPs ™
Electronic Standard Operating Procedures.
Available as Electronic SOPs on CD ROM
for immediate in-house use. Guidelines
provided on how to convert development
SOPs into your own customized researchbased-development system that meet allinternational regulatory guides, guidelines
and regulatory requirements. e-SOPs™
can be edited to meet your development
units own in-house needs. Designed forGeneric and NDA Drug Development use.
Electronic SOPs provide a complete
electronic Drug Development System,
including Decision Trees, Formulation,
Scale-up,
Process
Optimization&
Qualification; pivotal and final large scalevalidation batches; IQOQ, Analytical,
Cleaning
andProcess
Validation.
Essential technical documentation and
OGD regulatory know-how that is essential
for a successful product development anda speedy FDA approval, saving queuetime and development dollars.

Essential information for Development
Pharmacists, R&D Chemists, QA andRegulatory
personnel.
Allowsmanagement to understand the nuts andbolts on Generic ANDA and EC
DEVELOPMENT and filing in the most
cost effective way.
CD ROM or PRINT available at: $289
In association with theInternational Association of Generic Drug Manufacturers

Locum International Press
Locum Publishing House

handbooks@locumeuro.com

A Locum House Publication©Copyright LOCUM 1995 -2001

handbooks@locumusa.com

International Journal of Generic Drugs
ISSN 0793 694X US/Can
ISSN 0793 7784 EuroISSN 0793 7822 Pacific Rim

International Journal of Generic Drugs

H a n d b o o ko fPharmaceutical
Generic
Development
ISSN 0793 7601 -ISSN 0793 761X

Inhalation
Aerosols
Handbook Volume Consists of:Complete Drug Development
Complete ANDA Development

Part

ONE

DRUG Development Know-how

&

Part

TWO

ANDA Development Technology

The Handbook of Pharmaceutical
Generic Development is a practical
hand-on workbook covering the full 22
ANDA sections of ORAL & NASAL
Inhalation Aerosol (MDI Aerosol
solutions and suspensions).

Part One (Full Development ISBN 0793
7601) and Part Two (Detailed ANDA
Development covering all 22 Sections - ISSN
0793-761X)
provideDevelopment,
Formulation, Scale-up Process Qualification;
pivotal and final validation batches;analytical, cleaning and process validation;
essential
documentation
andOGD
regulatory know-how that is essential for a
successful review for a FDA approval,saving queue-time and money.

Essential development know-how on
Oral & Nasal Inhalation Aerosols for
professional developers to understand thenuts-and-bolts on Generic Dosage Form
DEVELOPMENT with high-tech detailed
ANDA development know-how to produce
flawless files. (Print & CD ROM). Presented
at an Advanced Technological Level.)E-mail:- h a n d b o o k s @ l o c u m u s a . c o m
Locum Internationa
Publishing House

A Locum House Publication©Copyright LOCUM 1996-1999

http://www.locum.co.il
International JournalofGeneric Drugs
e-* info@locum.co.il
ISSN 0793 694X US/Canada
ISSN 0793 7784 EuroISSN 0793 7822 Pacific Rim